Detection of EGFR Mutation in Malignant Pleural Effusion of Lung Cancer Patients and Cancer Cell Lines Establishment

NCT ID: NCT00752076

Last Updated: 2009-12-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-03-31

Brief Summary

1. Detection EGFR mutation of cancer cells from malignant pleural effusion. 2. Established the cancer cell lines with without EGFR mutation from malignant pleural effusion.

Detailed Description

Lung cancer is the leading cause of mortality in the world. Previous study has shown that about 88% lung cancer cases belong to non-small cell lung cancer (NSCLC) in Taiwan (1). Approximately 50~90% of NSCLC patients had expression (or described as overexpression) of EGFR in cancer (2,3). Although targeting the EGFR kinase domain using the inhibitors gefitinib (Iressa) and erlotinib (Tarceva) has no effect against solid tumors, it achieves impressive response in subgroup of NSCLC especially in Asian ethnic background, female sex, the absence of a history of smoking, and a tumor with histologic feature of adenocarcinoma (3,4,5). Molecular studies of highly responsive cases revealed high percentage of somatic mutation within the tyrosine kinase, ATP-binding domain of the EGFR gene (6). One possible explanation for this phenomenon is that the cancer cells are "addicted" to signaling via the mutant EGFRs and die when the mutant oncoprotein is inactivated (7). However, specific mechanisms underlying epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) induced cell death have not been well delineated (7).

Approximately 90% of mutations affect a few specific amino acids. In-frame deletions in exon 19 centered on codons 756 to 750 make up 45~50% of mutations, and another 35~45% consist of the missense mutation leucine to arginine at codon 858 (L858R) in exon 21 (8, 9, 10). The link between EGFR-TKI response and EGFR mutations have been confirmed, but the increased prevalence of mutations in Asian (25%to 50%) compared with North American and Western European patients (10%) is currently unexplained (6,8-12). The response rate to TKI treatment in mutations-positive is 77% (30% to 100% with most series >60%) compared with 10% in mutation-negative cases (6). It is interesting that exon 19 deletion have increased response and survival with TKIs compared with L858R cases (10, 13, 14). This is in contrast to the natural history of patients, where those with exon 19 deletions appear to have shorter survival than those with L858R (8). The biological difference is still unknown and different mutations may have different biochemical signaling properties (15).

In this study, we will collect the pleural effusion from lung cancer patients. We will characterize the EGFR status of the cancer cell from malignant pleural effusion and try to establish the cancer cell lines from these patients. We hope to establish several cell lines with different mutations and then we can compare the difference responses and signal pathways in these cell lines. We can also explore the detailed mechanism of TKI responsive cancer cell and try to develop other agent to enhance the pathways.

Conditions

NSCLC

Keywords

EGFR mutation; NSCLC cell line; Malignant pleural effusion

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

1

We collected malignant pleural effusion for NSCLC cell lines with different EGFR mutations development and then we can compare the difference responses and signal pathways in these cell lines. We can also explore the detailed mechanism of TKI responsive cancer cell and try to develop other agent to enhance the pathways.

Group Type: EXPERIMENTAL

cancer cell lines establishment

Intervention Type: OTHER

Detection of epithelial growth factor receptor (EGFR) mutation in malignant pleural effusion of lung cancer patients and cancer cell lines establishment

Interventions

cancer cell lines establishment

Detection of epithelial growth factor receptor (EGFR) mutation in malignant pleural effusion of lung cancer patients and cancer cell lines establishment

Intervention Type: OTHER

Other Intervention Names

EGFR mutation; NSCLC cell line establishment

Eligibility Criteria

Inclusion Criteria

• All malignant pleural effusion related to NSCLC between April 2008 and March 2009.
• Older than 18 years old.
• The patients who received thoracentesis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Chest medicine devision

Principal Investigators

Chao-Chi Ho, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Shang-Gin Wu, MD

Role: CONTACT

Phone: 0968661892

Email: b8501091@tmu.edu.tw

Chao-Chi Ho, PhD

Role: CONTACT

Phone: 886-2-23562905

Email: ccho1203@ntu.edu.tw

Facility Contacts

Shang-Chun Wu, MD

Role: primary

Chao-Chi Ho, PhD

Role: backup

Chao-Chi Ho

Role: primary

Ming-Tzer Lin

Role: backup

Other Identifiers

200804019R

Identifier Type: -

Identifier Source: org_study_id